ABSTRACT
Purpose: Our group demonstrated the safety, efficacy, and antiviral effect of intranasally administered Chlorpheniramine Maleate (CPM) for treating coronavirus disease 2019 (COVID-19). Since the nasal cavity is the portal of entry for COVID pathogens, sensory and upper respiratory symptoms (URS) (e.g., cough, ageusia, anosmia, nasal congestion, etc.) are significant symptoms in the course of the disease. Intranasal therapies could alleviate the disease-induced URS faster. This study evaluated the effectiveness and safety of intranasal CPM for treating mild to moderate COVID-19-induced URS in the outpatient setting. Methods: The two-part Accelerating COVID-19 Clinical Recovery in an Outpatient Setting (ACCROS) research study was conducted to collect evidence from a randomized, double-blinded placebo-controlled trial (ACCROS-I). Both parts enrolled patients with mild to moderate COVID-19 confirmed by reverse transcription-polymerase chain reaction. The primary endpoint in ACCROS-I was time to clinical recovery, defined as the change from baseline to day 7 in COVID-19 symptoms reported as the percent change (Δ%) in the daily symptoms score (DSS) and the severity of the disease symptoms using a visual analog scale (VAS), on a scale of 1-10 (10=worst symptoms). COVID-19 patients (n = 101) were recruited and assigned to either a 10-day CPM treatment (n=61) or placebo (PLB) (n=40) in addition to standard of care (SoC). Secondary endpoints included the incidence of hospitalization and the proportion of patients with URS on day 7. ACCROS-II data were collected from medical records of COVID-positive subjects using a standardized form. Cohorts of patients treated with CPM and SoC (CPM+Soc) were compared for the duration of general symptoms and URS. Patient information was collected as part of routine visits and telehealth consultations. Results ACCROS-I: There was a statistically significant difference in the rate of clinical recovery (P<0.05) in Δ%DSS (M -18.8±SEM 7.9%) and Δ%VAS (-8.6±5.1%), such that the CPM group reported fewer symptoms than PLB. The proportion of patients who reported sensory deficits and URS at day 7 was significantly lower (P<0.05) in CPM vs. PLB for ageusia (1.7% vs. 15.0%), cough (16.4% vs. 35.0%) and nasal congestion (8.1%vs.20%). None of the patients required hospitalization. ACCROS-II: There was a statistically significant reduction (P<0.05) in total days reporting URS for general symptoms of COVID-19 in CPM+SoC (5.1 ± 0.1) compared to SoC (11.0 ± 0.2). CPM+SoC users also showed fewer days with cough, anosmia, and ageusia. Persistent anosmia (over 29 days) was found in 3% of the patients on SoC, whereas no persistent anosmia was reported in the CPM+SoC cohort (X2 = 10.18; P<0.001). Conclusion: The result of this two-part study supports the conclusion that intranasal CPM is an antiviral agent that can be administered intranasally to treat COVID-19-induced symptoms effectively. Intranasal CPM accelerates clinical recovery and reduces URS in patients with mild to moderate COVID-19. This study's important implications include individuals returning to daily life faster, reducing community and individual economic burden, and decreasing healthcare utilization. Trial registration: ClinicalTrials.gov.; ID: NCT05449405 ACCROS-I retrospectively registered on 7/13/2022, NCT05520944 ACCROS-R retrospectively registered on 08/27/2022.
Subject(s)
COVID-19ABSTRACT
Background: COVID-19 pandemic has impacted lives globally. While COVID-19 did not discriminate against developed or developing nations, it has been a significant challenge for third world countries like Honduras to have widespread availability of advanced therapies. The concept of early treatment was almost unheard-of when early outpatient treatment with repurposed drugs in Latin American countries showed promising results. One such drug is fluvoxamine, that has shown tremendous potential in two major studies, following which fluvoxamine was added to the standard of care in Honduras. Methods: This is a prospective observational study performed at the Hospital Centro Medico Sanpedrano (CEMESA) in San Pedro Sula, Cortes, Honduras in the COVID-19 outpatient clinic. All patients fifteen years of age or older, with mild or moderate signs and symptoms of COVID-19, and a positive SARS-CoV-2 antigen or Reverse Transcription Polymerase Chain Reaction (RT-PCR) were included in the study and prescribed fluvoxamine. Cohort of patients who decided to take fluvoxamine were compared to the cohort who did not take fluvoxamine for mortality risk and risk of hospitalization as primary endpoints. Patient were monitored for 30 days with first follow up at 7 days and second follow up at 10-14 days of symptom onset. Categorical variables were compared by Pearson Chi-square test. The Odds ratio was calculated using univariate and multivariate logistic regression. Continuous variables were compared by t-test and Wilcoxon rank-sum tests. Results: Of 657 total COVID-19 cases, 594 patients took fluvoxamine and 63 did not. A total of five patients (0.76 percent) died, of which only one death occurred in the fluvoxamine group. Patients who did not receive fluvoxamine had a significantly higher mortality (OR 24, p0.005, CI 2.6 to 233.5). Odds ratio of hospitalization in patients who did not take fluvoxamine was 2.38 (30 vs 10 hospitalizations, p 0.040, CI 1.04-5.47). The odds ratio of requiring oxygen in patients in the non-fluvoxamine group was 5.08 (p<0.001, CI 2.18- 11.81). Mean lymphocytes count on the first follow-up visit was significantly higher in the fluvoxamine group (1.72 vs. 1.38, {Delta} 0.33, p 0.007, CI 0.09 to 0.58). Conclusion: The results of our study suggest lowers odds of mortality and hospitalization in patients who took fluvoxamine vs fluvoxamine non-takers. Non-fluvoxamine group had higher odds of oxygen requirement than fluvoxamine group as well.